RNAs that make your heart beat

Hyptertension_MicroRNAs_700x233

Love, life, health and vitality. All are connected through one symbol: the beating of a heart. Often we don’t notice the strength of this organ until it starts to beat fast enough in our chests that we can feel it. One of the most beautiful instances of a racing heart happens during social bonding and when we fall in love, which can be triggered by the so-called “love hormones,” such as oxytocin (1). A rapid rise in oxytocin levels can cause variations in how our heart beats, which is a good indicator of a person’s motivation for social behavior (2). Amazingly, there are even studies showing that the heart rates of a couple can sync up (3). Isn’t that a romantic thought for Valentine’s Day?

In general, our heartbeat increases when our body requires more oxygen, and it’s a sign of health and vitality; however, certain disorders like arrhythmias can be characterized by an irregular heartbeat. Fascinatingly, the ability of the heart to beat relies on the conversion of an electrical signal into a mechanical response (4). The cardiac cycle begins at the sinoatrial node, which is a mass of cells that set the pace of the heart. Here, the electrical signal starts in the form of an action potential, before being transmitted to the atrial and ventricular heart muscle cells (cardiac myocytes) via the passage of ions through gap junctions. Those ions flow into and out of the cardiac myocytes through voltage-gated channels, depolarizing the membrane potential and thereby allowing another set of different channels to open. Opening and closing of these channels induces conformational changes that make the heart beat – and most of these channels and mechanisms are regulated by changes in gene expression. One of the most well-known channels involved in this process is specific for potassium.

Unraveling complexity

The regulation of potassium channels occurs through several mechanisms, including transcriptional regulation, splicing, RNA editing and post-translational phosphorylation (5–7). Additionally, evidence shows that miRNAs (small single-stranded, endogenously-encoded RNAs) can function as post-transcriptional regulators of potassium channels (5) and play a role in responding to cardiac stress and controlling heart function (5–7).

The importance of miRNAs in maintaining a healthy heart has been demonstrated by deleting either Dicer or Dgr8 in cardiac myocytes (8–9). miRNAs were shown to not only affect the survival of these cells, but also to specifically target mRNAs encoding ion channels. Mouse studies of miR-1 genes show that homozygous deletion of one of two miR1-genes (miR-1-2) leads to 50% lethality by weaning, and most of the survivors die from sudden cardiac arrest caused by arrhythmias (10). Other findings indicate that miR-1 regulates a transcriptional repressor of a potassium voltage-gated channel component (10), and even post-transcriptionally represses a specific subfamily of those channels (Kcnh2), which encodes the potassium channel subunit (Kir2.1). This component encodes connexin 43, which is important for cardiac gap junctions (11). In addition to its role in regulating action potentials, miR-1 is known to aggravate arrhythmias; however, in rats undergoing myocardial infarction, antisense inhibitors of miR-1 reduce arrhythmias (11). Unraveling the functional relevance of miRNAs in pathogenic pathways is a major challenge, which is why we offer miScript miRNA PCR Arrays for pathway-focused PCR profiling of miRNA involved in cardiovascular diseases from different species.

Find the perfect combination

This Valentine’s holiday, get reliable gene expression profiles by pairing together our RNeasy Plus Kitsfor highly pure RNA extraction, with our QuantiNova Kits, for fast and specific RT-qPCR on any real-time cycler. To find out more about QIAGEN’s perfect combinations for mRNA or miRNA gene expression and the dedicated services we offer for profiling pathway- or disease-specific miRNAs or whole miRNomes and pathway-focused PCR array services, visit the Life Science Service Core.


References:

    • 1. Magon, N. and Kalra, S. (2011) The orgasmic history of oxytocin: Love, lust, and labor. Ind. J. Endocrinol. Metab. 15, S156–S161. Link
    • 2. Kemp, A.H., Quintana D.S., Kuhnert, R., Griffiths, K., Hickie, I.B., Guastell, A.J. (2012) Oxytocin increases heart rate variability in humans at rest: implications for social approach-related motivation and capacity for social engagement. PLOS One. 7, 8. Link
    • 3. Ferrer, E. and Helm, J.L. (2013) Dynamical systems modeling of physiological coregulation in dyadic interactions. Int. J. Psychophys. 88, 296–308. Link
    • 4. Grant, A.O. (2009) Cardiac ion channels. Circ. Arrhytm. Electrophysiol. 2, 185. Link
    • 5. Yang, K.C. and Nerbonne, J.M. (2016) Mechanisms contributing to myocardial potassium channel diversity, regulation and remodeling. Trends Cardiovasc. Med. 26, 209–18. Link
    • 6. Schmitt, N., Grunnet, M. and Olesen, S.P. (2014) Cardiac potassium channel subtypes: new roles in repolarization and arrhythmia. Physiol. Rev. 94, 609–53. Link
    • 7. Kim, G.H. (2013) MicroRNA regulation of cardiac conduction and arrhythmias. Transl. Res. 161, 381–92. Link
    • 8. da Costa Martins, P.A., Bourajjaj, M., Gladka, M. et al. (2008) Conditional dicer gene deletion in the postnatal myocardium provokes spontaneous cardiac remodeling. Circulation 118, 1567–76. Link
    • 9. Rao, P.K., Toyama, Y., Chiang, H.R. et al. (2009) Loss of cardiac microRNA-mediated regulation leads to dilated cardiomyopathy and heart failure. Circ. Res. 105, 585–94. Link
    • 10. Zhao, Y., Ransom, J.F., Li, A. et al. (2007) Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. Cell 129, 303–17. Link
    • 11. Yang, B., Lin, H., Xiao, J. et al. (2007) The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2. Nat. Med. 13, 486–91. Link

 

Laura Alina Mohr, M.Sc.

Laura Alina Mohr joined QIAGEN in 2015. She received her Master’s Degree in Chemical Biology at the Technical University Dortmund in Germany. During this time, she was involved in Systemic Cell Biology research at the prestigious Max Planck Institute. Before joining QIAGEN, Laura Alina worked at the Scripps Research Institute, San Diego, where she first focused on DNA damage/repair pathways and telomere biology. Later, she joined the Muscle Development, Aging and Regeneration program at the Sanford Burnham Prebys Medical Discovery Institute. At QIAGEN she is interested in gene expression profiling focusing on various biological pathways, e.g. cancer research and neurodegeneration.

Your email address will not be published. Required fields are marked *